| Project/Area Number |
17K08850
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | インフルエンザウイルス / 宿主因子 / ウイルスゲノム複製 / RNA依存性RNAポリメラーゼ / インフルエンザ / ウイルス複製 / 感染種特異性 / タンパク質構造 |
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| Outline of Final Research Achievements |
In this study, we performed structural analyses to clarify the activation mechanism of host factor, pp32 which regulates the genomic RNA replication of influenza virus, as follows.
By domain analyses using human pp32 protein, essential regions for the activation of the viral RNA replication and also, interaction with viral RNA polymerase were determined. Further, a partial crystal structure of pp32 were newly determined in this study, and several point mutants of pp32 were designed and constructed based on the crystal structure. As the result of evaluating the stimulation activity of the point mutants of pp32 employing cell-free viral RNA replication assay, certain point mutants of pp32 were shown to be defective on the stimulation activity. These line of these point mutant analyses would provide a important clue for understanding the mechanism of stimulatory activity for the influenza viral RNA replication by the host-derived factor pp32.
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| Academic Significance and Societal Importance of the Research Achievements |
宿主因子pp32についての一連の変異体解析の結果から、インフルエンザウイルスゲノム複製に対する宿主因子pp32の促進メカニズムが推測できる。pp32は酸性アミノ酸に富むC末端ドメインでウイルスポリメラーゼに結合した後に、中間ドメインにおける構造変化によってウイルスポリメラーゼのRNA複製開始が促進される可能性を考察している。
本研究により得られた結果・考察は、現在活発なインフルエンザウイルスポリメラーゼの構造学的解析の流れとともに、多様なウイルスポリメラーゼ活性を理解するための重要な基盤情報を与えてくれる。さらには創薬、ウイルス耐性家畜のデザイン等の「抗ウイルス戦略」への応用が期待される。
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